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Inhibitory effects of long-term administration of ferulic acid on astrocyte activation induced by intracerebroventricular injection of beta-amyloid peptide (1-42) in mice.

Cho, JY; Kim, HS; Kim, DH; Yan, JJ; Suh, HW; Song, DK
Progress in neuro-psychopharmacology & biological psychiatry, 29(6):901-907, 2005
Journal Title
Progress in neuro-psychopharmacology & biological psychiatry
Accumulating evidence indicates that glial cells are actively involved in the pathogenesis of Alzheimer's disease. We recently reported protective effects of long-term administration of ferulic acid against learning and memory deficit induced by centrally administered beta-amyloid peptide (Abeta)1-42 in mice. In that report, we found that the Abeta1-42-induced increases in immunoreactivities of glial fibrillary acidic protein, the astrocyte marker, and interleukin(IL)-1beta in the hippocampus are also suppressed by pretreatment with ferulic acid. In the present study, we aimed to further characterize the effect of long-term administration of ferulic acid on the centrally administered Abeta1-42-induced activation of glial cells in mice. Mice were allowed free access to drinking water (control) or water containing ferulic acid (0.006%) for 4 weeks, and then Abeta1-42 (410 pmol) was administered via intracerebroventricular injection. Intracerebroventricularly injected Abeta1-42 induced an increase in immunoreactivities of endothelial nitric oxide synthase (eNOS) and 3-nitrotyrosine (3-NT) in the activated astrocytes in the hippocampus. Pretreatment of ferulic acid for 4 weeks prevented the Abeta1-42-induced increase in eNOS and 3-NT immunoreactivities. Administration of ferulic acid per se induced a transient and slight increase in eNOS immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. Intracerebroventricularly injected Abeta1-42 also increased interleukin-1alpha(IL-1alpha) immunoreactivity in the hippocampus, which was also suppressed by pretreatment with ferulic acid. These results demonstrate that long-term administration of ferulic acid induces suppression of the centrallly injected Abeta1-42-induced activation of astrocytes which is suggested to underlie the protective effect of ferulic acid against Abeta1-42 toxicity in vivo.
MeSH terms
Amyloid beta-Peptides/administration & dosage*Amyloid beta-Peptides/antagonists & inhibitorsAnimalsAstrocytes/drug effects*Astrocytes/metabolismCell Count/methodsCoumaric Acids/administration & dosage*Drug InteractionsFree Radical Scavengers/administration & dosage*Gene Expression Regulation/drug effectsGlial Fibrillary Acidic Protein/metabolismHippocampus/cytologyHippocampus/drug effectsImmunohistochemistry/methodsInjections, Intraventricular/methodsInterleukin-1/metabolismMaleMiceMice, Inbred ICRNitric Oxide Synthase/metabolismNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPeptide Fragments/administration & dosage*Peptide Fragments/antagonists & inhibitorsTime FactorsTyrosine/analogs & derivativesTyrosine/metabolism
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